AB0346 REASONS FOR DISCONTINUATION OF TNF INHIBITORS IN PATIENTS WITH DIFFICULT-TO-TREAT RHEUMATOID ARTHRITIS ACCORDING TO DRUG HISTORY
Authors: E. Matianova, A. Gordeev, E. Galushko
Journal: Annals of the Rheumatic Diseases (2022)

Background TNF-alpha inhibitors (TNFi) are considered the drugs of choice for initiating biological therapy in rheumatoid arthritis (RA). Rreview of the reasons for their cancellation is included in a comprehensive study of the group of patients (pts) with Difficult to Treat RA (D2T). Objectives To make a comparative assessment of the reasons for discontinuation of TNFi in pts meeting the international EULAR (2021) criteria for D2T, comparing them with other pts who had experience in taking a biological disease modifying antirheumatic drugs (bDMARDs)/targeted synthetic DMARDs (tsDMARDs). Methods We analyzed the drug history of 505 pts with RA who were hospitalized at the V.A.Nasonova Research Institute of Rheumatology hospital from January to December 2021(inclusive) due to an RA exacerbation, and who were approved for the introduction of bDMARD/tsDMARD. Pts with no prior experience with bDMARD/tsDMARD were excluded from the analysis (n=179/35.4%). Pts meeting the EULAR criteria for D2T RA (the main of which: failure of two or more bDMARDs/tsDMARDs of different mechanisms of action) were allocated to the D2T group (n=35/6.9%), the rest of the pts made up the control group C (n=291/57.6%). The middle age (±SD) of patients in D2T was less than in C (D2T - 46.3±15.1 years vs. C - 51.6±14.8 years, p=0.047), the duration of RA in the groups was comparable (D2T - 15 .7±10.7 years vs. C – 13.1±8.9 years, р&gt;0.05). Results The frequency of prescribing a history of TNFi in D2T (85.7%) was higher than in C (38.5%; OR=2.9 [1.3-6.6]; p&lt;0.0001). The total duration of their intake (in cases of prescription) and the average number of TNFi drugs in the groups were comparable (p&gt; 0.05), but in D2T pts more often had the experience of taking 3 or more TNFi (OR = 6.4 [2 -20.4]; p=0.002) (Table 1). Table 1. Reasons for discontinuation of TNFi in study groups (n/%) D2T (n=35 ) C (n=291 ) р Pts taking TNFi in anamnesis, n/% 30 / 85,7 112 / 38,5 &lt;0,0001; OR=9,6 [3,6-25,4] Total duration of taking TNFi М±SD, Me [25; 75 percentile], months 22,8±22,5* 15[6;35] 23,2±27,5*11[4;34] &gt;0,05 Pts taking 3 or more TNFi, n/% 8 /26,7* 6 /5,4* 0,002; OR=6,4 [2-20,4] Cancellation for administrative reasons, n/% 2 /6,7* 37 /33* 0,004 CHI-Square ;OR=6,9 [1,6-36,6] Adverse reactions, n/% 9 /30* 23 /20,5* &gt;0,05 insufficient efficiency Total 28 /93,3* 49 /43,8* &lt;0,0001 CHI-Square ; OR=18 [4,1-79,3] Secondary non-responsiveness to TNFi 17 /56,7* 35 /31,3* 0,01; OR=2,9 [1,3-6,6] Gradual fading effect 7 /41,2** 22 /62,9** &gt;0,05 After the break 9 /52,9** 7 /20** 0,02; OR=4,5 [1,3-15,9] After changing to generic 1 /5,9** 7 /20** &gt;0,05 *the percentage is calculated from the number of pts who took TNFi **percentage calculated from the number of pts with a history of secondary efficacy of any TNFi Withdrawal of TNFi due to their ineffectiveness was more often performed in D2T (93.3%/n=28) than in C (43.8%/n=49; OR=18 [4.1-79.3];p&lt;0.0001). At the same time, secondary non-responsiveness (NR) prevailed in D2T - in 56.7% (17 of 28 cases of NR), which is more often than in C (31.3% / 35 of 49 cases of NR; OR = 18 [4.1-79.3]; p&lt;0.0001). Secondary NR in D2T in 59.9% of pts (9 of 17 cases of secondary NR) developed after the break for administrative reasons in taking a previously effective drug, which is significantly more common than in C (20%/7 of 35 cases of secondary NR; OR = 4.5 [1.3-15.9], p=0.02). Withdrawal of TNFi for administrative reasons was more common in C (33%/n=37 vs. in D2T -6.7%/n=2; OR=6.9 [1.6–36.6]; p =0.004). The incidence of adverse reactions in both groups was comparable (in D2T 30%/n=9 vs. in C - 20.5%/n=23; p&gt;0.05). Conclusion In patients with D2T RA, TNFi were discontinued more often due to their ineffectiveness (93.3%; compared with C: p&lt;0.0001). This inefficiency was more often secondary (56.7%; compared with C: p=0.01). In the structure of secondary inefficiency, the variant of its development after a break in reception for administrative reasons prevailed (52.9%; compared with C: p=0.02). The incidence of adverse reactions in both groups was comparable. Disclosure of Interests None declared